The field of the disclosure relates generally to a potent and specific oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) inhibitor and to methods of administering the inhibitor for treating autoimmune diseases, and in particular, to treating glomerulonephritis-associated diseases such as systemic lupus erythematosus (SLE).
Systemic lupus erythematosus (SLE), a multi-systemic autoimmune disease with a prevalence in about 40-200/100,000 persons, is thought to be caused by multiple pathogenic responses, including genetic, environmental, hormonal, epigenetic, and immunoregulatory factors, that either sequentially or simultaneously affect the immune system. Action of these pathogenic factors results in generation of autoantibodies, immune complexes, autoreactive or inflammatory T cells, and inflammatory cytokines that, together, lead to amplification of inflammatory signaling pathways and damage to vital organs (e.g., skin, kidneys, spleen, heart, thymus, lymph nodes, joints, and nervous system).
Cytokines such as IL-6, IL-4, IL-5 and IL-10 are overproduced in lupus patients. Aberrant regulation of cytokines, such as IL-6, IL-10, IL-17, type I interferon (IFN) and tumor necrosis factor-α (TNF-α), are closely linked to pathogenesis of SLE, playing key roles in the regulation of systemic inflammation, local tissue damage, and immunomodulation. However, the specific signaling mechanisms that cause SLE remain elusive and current therapeutic strategies primarily target the symptoms and not the disease itself.
Accordingly, there is a continuing need for new therapeutic compounds and methods of treating glomerulonephritis-associated diseases such as SLE.